Histamine H4 receptor (H4R) has become a promising target for immuno-inflammatory diseases, such as allergic rhinitis, asthma or dermal allergies. Its distribution pattern in immune cells and the preclinical data obtained from different biological systems using diverse histamine H4 modulators (1) suggest a key role of H4R in immunity and in inflammatory cell trafficking. Recent results with UR-63325, the first H4R antagonist from which clinical data has been reported (2), confirm the feasibility of complete H4R blocking in humans without limiting safety concerns. Also, H4R blockade results in clear pharmacodynamic effects in relevant human cells, e.g. eosinophils. It is believed that allergic rhinitis and asthma are manifestations of one unique syndrome in two parts of the respiratory tract. Dermal allergies are also recognized as related manifestations in a different location. The coexistence of allergic-related diseases in the same patients could permit a single treatment approach e.g.. the systemic use of H4R antagonists. Further clinical studies are needed to establish the role of H4R antagonists in the treatment of allergic diseases.